#1783144 Tumor Induced Osteomalacia - A Case Series

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23 secreting tumors. Excessive production of FGF23 causes hypophosphatemia through increased excretion and decreased absorption of phosphorus. This leads to decreased bone density, bone pain, muscle weakness, impaired gait, and recurrent fractures. The purpose of this case series is to present three unique cases, each with its own challenges. Retrospective Case Series In this case series, we present three patients with either confirmed or presumed diagnoses of TIO. These patients presented to endocrinology with insufficiency fractures and bone pain. Due to the rarity of this disease and seemingly non-specific symptoms, each of their timelines noted a delay in time to diagnosis. In two of our patients, the delay led to life-altering fractures and weakness. Laboratory evaluation demonstrated hypophosphatemia, elevated or inappropriately high normal FGF23 levels, and elevated fractional excretion of phosphorus in urine. However, this constellation was not identified for months. One underwent genetic testing to rule out genetic causes of FGF23-driven hypophosphatemia. Two of these patients underwent PET-DOTATATE imaging. Imaging findings led to identification of tumor source and curative surgical resection in one. Another had multiple sites with increased uptake, most notably an unresectable region in the lumbar spine. The radiolabeled imaging study is pending on our third patient, awaiting insurance approval. Given their clinical and laboratory findings, two of the patients were started on Burosumab. Only one patient remains on it, as the other stopped following tumor resection. Both treated patients reported symptomatic improvement. The third patient has not been able to start due to coverage challenges. The results of our case series reveal one alarming factor: delays in diagnosis and treatment. Our patients have suffered progression of disease due to (1) failure to obtain correct diagnosis; (2) failure to access diagnostic imaging due to insurance restrictions; and, (3) challenges in obtaining disease-specific treatments. While definitive cure for TIO can be achieved with complete surgical resection of the tumor, patients can have symptomatic and reversal of hypophosphatemia with Burosumab. Evaluation of phosphorus levels needs to be considered in cases of recurrent insufficiency fractures. FGF23 levels and a urinary fractional excretion of phosphorus should be obtained to complete the work up for osteomalacia. When clinical and laboratory presentation is highly suspicious for the disease, appropriate imaging should be performed to identify the location of the tumor. Early diagnosis and rapid initiation of treatment may prevent progression of disease and significant debilitation.